Effect of lappaconitine on neuropathic pain mediated by P2X3 receptor in rat dorsal root ganglion
Effect of lappaconitine on neuropathic pain mediated by P2X3 receptor in rat dorsal root ganglion
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DOI：
10.1016/j.neuint.2011.01.016
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发表时间：
2011-04-01
影响因子：
4.2
通讯作者：
Ruan, Huai-Zhen
中科院分区：
文献类型：
--
作者：
Ou, Shan;Zhao, Yan-Dong;Ruan, Huai-Zhen
ATP通过P2 X受体（尤其是P2 X亚型）促进背根神经节（DRG）水平神经性疼痛的引发和传递（3）。高乌甲素（Lappaconitine，LA）是从中草药中提取的一种有效成分，具有镇痛作用.本研究旨在探讨LA对慢性压迫性损伤（CCI）所致神经病理性疼痛的影响，并通过背根神经节（DRG）神经元P2 X（3）受体介导LA对CCI所致神经病理性疼痛的影响。在CCI和/或LA存在的情况下，测量机械撤回阈值（MWT）和热撤回潜伏期（TWL），并通过免疫组织化学和Western blotting检测DRG神经元P2 X（3）受体的表达。鞘内注射P2 X（3）受体寡核苷酸后，评估LA对痛阈的影响。此外，在急性分离的大鼠DRG神经元上，用全细胞膜片钳技术研究了LA对P2 X（3）受体激动剂ATP和α，β-meATP诱导的内向电流（I-ATP和I-alpha，I-beta-meATP）的影响。结果包括：（1）神经病理性痛时，痛阈降低，I-ATP和I-alpha，I-beta-meATP含量增加，P2 X（3）受体表达上调。(2)在LA存在下，CCI大鼠痛阈降低、P2 X（3）受体表达上调、I-ATP和I-alpha，I-beta-meATP增加是可逆的。(3)P2 X（3）受体反义寡核苷酸预处理可下调P2 X（3）受体表达，显著减弱LA的镇痛作用。上述结果提示，LA的镇痛作用与抑制CCI后大鼠DRG神经元P2 X（3）受体的表达和致敏有关。(C)2011爱思唯尔有限公司版权所有。
ATP facilitates initiation and transmission of the neuropathic pain at the dorsal root ganglion (DRG) level via the P2X receptors, especially the subtype P2X(3). Lappaconitine (LA) is an active principle isolated from Chinese herbal medicine and possesses analgesic effect. The aim of this study was to investigate the effect of LA on chronic constriction injury (CCI)-induced neuropathic pain mediated by P2X(3) receptor in the DRG neurons. In the presence of CCI and/or LA, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured and P2X(3) receptor expression in the DRG neurons was evaluated by immunohistochemistry and Western blotting. Following intrathecal administration of P2X(3) receptor oligonucleotide, the effect of LA on pain thresholds was assessed. Furthermore, the effect of LA on the P2X(3) receptor agonists ATP- and alpha,beta-meATP-induced inward currents (I-ATP and I-alpha,I-beta-meATP) in the acutely dissociated rat DRG neurons was investigated by whole cell patch-clamp. The results included: (1) There showed reduction of pain thresholds, enhancement of I-ATP and I-alpha,I-beta-meATP and up-regulation of P2X(3) receptor expression in rat DRG neurons when neuropathic pain occurred. (2) In the presence of LA, the decreased pain thresholds, the up-regulated P2X(3) receptor expression and the enhanced I-ATP and I-alpha,I-beta-meATP were reversible in the CCI rats. (3) The down-regulated P2X(3) receptor expression with pretreatment of P2X(3) receptor antisense oligonucleotide significantly attenuated the analgesic effect of LA. These results indicate that the analgesic effect of LA involves decrease of expression and sensitization of the P2X(3) receptors of the rat DRG neurons following CCI. (C) 2011 Elsevier Ltd. All rights reserved.